Clapp, LH;
Patel, J;
(2010)
The mechanistic basis for prostacyclin action in pulmonary hypertension.
[Review].
International Journal of Respiratory Care
, 6
(1)
pp. 27-33.
Preview |
Text
Clapp & Patel 2010.pdf - Published Version Download (298kB) | Preview |
Abstract
Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries in which patients suffer from elevated pulmonary arterial pressure, right ventricular failure and a reduction in gas exchange. Left untreated the median survival from diagnosis is ~2.8 years, though outcome is significantly worse if patients have underlying pulmonary fibrosis or scleroderma. Injury to the endothelium probably initiates the disease process, with increased production of vasoconstrictors (endothelin and thromboxane) and growth factors accompanying the loss of vasodilator and anti-platelet agents, prostacyclin and nitric oxide, which results in vascular remodelling. To date prostacyclin therapy still remains the most efficacious treatment for PAH, although its short half-life and cumbersome delivery (continuous infusion) meant analogues with improved stability and alternative routes of delivery were developed. Classically, prostacyclin agents are thought to produce haemodynamic and anti-proliferative effects through prostacyclin (IP) receptors coupled to cyclic AMP generation, though other prostanoid receptors may contribute (EP2, EP4) or counterbalance (EP1, EP3) these responses. Increasing evidence suggests peroxisome proliferator-activated receptors (PPARs) are also cellular targets for prostacyclin agonists, regulating cell growth, inflammation and apoptosis through these transcription factors. Activation involves ligand binding and/or membrane receptors but probably not cyclic AMP. Here we discuss recent advances in our understanding of PPARs and how they may represent an important therapeutic target in PAH
Archive Staff Only
 |
View Item |
